Following limb amputation, suspension-type attachment of an exoprosthesis to the residual limb is currently the standard of care, but is not suitable for every patient. For example, suspension technology fails with patients with short residual limbs, whom experience persistent deterioration of soft tissues, and/or hampered by exuberant heterotopic ossification. It is for these patients that Percutaneous Osseointegrated Docking Systems (PODS) are being developed worldwide so they can attach their exoprosthesis directly to the bone of their residual limb. In Europe, thre primary groups are working with human volunteer amputees to investigate PODS technology. However, these European PODS are not currently FDA approved for use in the United States, in part, because they lack evidence of an infection-free biological seal between the periprosthetic tissues and the PODS device. Here in the United States, our team has worked since 2006 on the design, the development, and the evaluation of a new type of PODS device. We have shown that endoprosthetic PODS devices, incorporating porous-coated titanium subdermal barriers, have the ability to inhibit infection by maintaining a biologically attached epithelial seal in load-bearing animals for at least 12- months. However, within the first 12-weeks post-implantation, the periprosthetic tissues surrounding the PODS device << exhibit a chronic wound healing response and >> migrate along the percutaneous interface, possibly in an attempt to make the device extra-cutaneous, a process known as down growth. This is of concern because << down growth breaks the biologically attached epithelial seal, creating a gap >> between the periprosthetic tissues and the PODS device, a direct conduit for microbial invasion - one that can lead to local, or even systemic infection. << To maximize the functional recovery of patients with amputated limbs, we >> need to establish, to maintain, and if necessary, to re-establish a non-migratory biological seal between the periprosthetic tissues and the PODS device. Clinically, chronic wounds are often closed using a technique known as Vacuum Assisted Closure (VAC) therapy, << also known as Negative Pressure Wound Therapy (NPWT) >>. We will first determine if << NPWT can inhibit the down growth >> and subsequent infection of the periprosthetic tissues surrounding PODS devices. Second, we will establish whether << NPWT >> is required to maintain the biological seal over time. Third, in the << presence of a gap between the periprosthetic tissues and the PODS device >>, we will determine whether NPWT can re-establish the biological seal between the periprosthetic tissues and the PODS device. The results from this study will facilitate the safe clinical introduction of percutaneous osseointegrated prostheses, improving the quality of life for patients in the VA, military, and broader civilian populations with severe limb injuries.